Myocardial infarction (MI) is a serious public health problem affecting 1.5 million Americans each year. Despite advances in treatment, the one year survival rate following MI is only 37%. Furthermore, the patients who survive still suffer irreversible loss of heart function due to cardiomyocyte death and subsequent scarring of the heart. These patients often progress to congestive heart failure, which is a growing epidemic and economic burden on the health care system. Silver Creek Pharmaceuticals is developing protein therapeutics to regenerate functional heart tissue after myocardial infarction. We use a combination of computational and experimental biology to design growth factor based drugs called Smart Growth Factors (SGFs) that can act selectively on damaged cardiomyocytes to stimulate their survival. We have a proof of concept molecule that significantly preserves functional heart tissue in a rat model of MI. This molecule is a fusion of a growth factor and a cellular targeting arm to a scaffold protein. The explicit contributions of the targeting arm and te scaffold to the molecule's mechanism of action are unknown. In Phase I of this program we aim to learn more about how the design of the molecule contributes to its function by designing, building and testing SGF variants that systematically explore the effect of each molecule component on SGF function. The understanding gained from these tests will enable the design of even more effective therapies, which will be tested in expanded efficacy studies in Phase II.